This project will develop a radically new photonic band-gap resonator technology that would increase sensitivity of Electron Paramagnetic Resonance (EPR) spectroscopy for studies of biological samples. This new technology is envisioned to have a broad applicability across the many fields where EPR is currently employed by biomedical researchers ? from structure and dynamics of biological macromolecules and complexes to microimaging and detecting and characterizing free-radical species. The overreaching goal is to resolve the main bottleneck of EPR instrumentation when applied to liquid aqueous samples ? the natural environment in which biological molecules and cells perform their functions. The main problem of studying such samples by EPR is a non-resonant absorption of the mm-wave field by water that ultimately limits the volume of EPR sample and also is a cause for microwave heating. These problems only worsen as the EPR resonant frequency increases with the magnetic field, thereby adversely affecting any gain in sensitivity potentially attainable with field/high frequency EPR ?an emerging method with superior spectral resolution. The primary objective of this exploratory research grant is to demonstrate that one-dimensional photonic band-gap structures are suitable for an effective separation of the electrical and magnetic field components of mm-waves while achieving exceptionally high quality factors Q=500-1,000 even with lossy aqueous samples with volumes of at least several microliters. It is hypothesized that the proposed structures will maximize the product of Q and the resonator filling factor while yielding at least an order in magnitude improvement in EPR sensitivity vs. state-of-the-art. The approach involves both electromagnetic simulations and constructing a W-band (95 GHz) photonic band-gap resonator for CW EPR and testing its performance for a series of biomolecules labeled with nitroxides and Gd(III) ions. Further, the design will be optimized for pulsed EPR and then scaled up to ca. 190- 200 GHz resonant frequency. This project is viewed as a first step towards further expanding the applicability of high-field/high-frequency EPR in NIH research. Future directions of this project will utilize large sample volume of photonic band-gap resonators for their integration with dynamic nuclear polarization (DNP) instrumentation for a dramatic enhancement of NMR signals at physiologically relevant conditions and temperatures, including membrane proteins in native lipid bilayers, cellular organelles, and, potentially, living cells.